The clinical usefulness of once weekly GLP-1 receptor agonists, dulaglutide (D) and semaglutide (S), on domestically approved doses in Japan, was assessed by the multicenter RCT to compare the efficacy, safety and patient satisfaction of D at a dose of 0.75mg and S at a dose of 0.25-1.0mg in patients with type 2 diabetes. The study protocol was approved by the IRB of Kawasaki Medical School (No.5276-01). A total 120 patients eligible for the criteria with HbA1c of 7% or more were randomly assigned to groups D and S (D:S = 59:61), and 107 subjects completed the trial for 24 weeks (D:S=53:54). Backgrounds of 107 subjects were age 62.7 ± 10.7 years, disease duration 13.9 ± 7.4 years, BMI 29.3 ± 5.9 kg/m2, HbA1c 8.0 ± 0.6%. There were no differences in these parameters between 2 groups. Dose of S was escalated by 4 weeks from 0.25mg to adequate dose for each, and average dose was 0.63±0.24mg. The primary endpoint was the difference of HbA1c level between 2 groups at 24 weeks. The HbA1c level at 24 weeks was significantly lower in S than D (D: 8.1±0.6→7.4±0.8 vs S: 7.9±0.5→ 6.7±0.5%, p<0.0001). Reduction in BMI and VFA levels were also more significant in S (D vs. S), BMI: 29.2→28.8 vs. 29.4→28.1 kg/m2, VFA: 174.5→164.6 vs. 175.8→153.2cm2, respectively (p< 0.05). The achievement rate of HbA1c <7% was higher in S (D vs S; 30.8% vs 70.4%, p<0.0001). The parameters such as LDL-C, ALT, γGTP, and apo B/A1 were decreased, and the L/S ratio was increased only in S. Compared the changes in L/S ratio less than 0.9 at baseline, which is diagnosed as NAFLD by CT, between two groups, the ratio was significantly elevated only in the S, but not in D at 24weeks. Gastrointestinal symptoms were observed in 13.2% of D and 46.3% of S (p<0.01). DTR-QoL scores related to pain and gastrointestinal symptoms were superior in D. This prospective trial demonstrated that S has more pronounced effects on glucose and BMI lowering, as well as a reduction in liver fat percentage and visceral fat area. Disclosure T. Kimura: Speaker's Bureau; Sanwa Kagaku Kenkyusho, Kowa Research Institute, Inc., Taisho Pharmaceutical Holdings Co., Ltd., Boehringer Ingelheim Japan, Inc., Sumitomo Dainippon Pharma Co., Ltd., Sanofi, MSD Life Science Foundation, Lilly, Daiichi Sankyo, Novo Nordisk. Y. Katakura: Speaker's Bureau; Abbott. M. Shimoda: Speaker's Bureau; Sanofi, Lilly, AstraZeneca, Ono Pharmaceutical Co., Ltd., Kowa Company, Ltd., Novo Nordisk, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., MSD Life Science Foundation, Mitsubishi Tanabe Pharma Corporation. F. Kawasaki: None. M. Yamabe: Speaker's Bureau; Novo Nordisk, Eli Lilly Japan K.K., Abbott Japan Co., Ltd., Sanofi, Boehringer Ingelheim Japan, Inc., Kowa Company, Ltd., Ono Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Sumitomo Dainippon Pharma Co., Ltd., Terumo Corporation. F. Tatsumi: Speaker's Bureau; Abbott Japan Co., Ltd., Kowa Company, Ltd., Novo Nordisk. M. Matsuki: None. Y. Iwamoto: Speaker's Bureau; Kowa Company, Ltd. T. Anno: None. Y. Fushimi: None. S. Kamei: None. Y. Kimura: None. J. Sanada: Speaker's Bureau; Lilly, Kowa Company, Ltd. Y. Hirata: None. S. Nakanishi: Speaker's Bureau; Boehringer Ingelheim Japan, Inc., Novo Nordisk, Sanofi, Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Daiichi Sankyo, Kowa Company, Ltd., Abbott, Mitsubishi Tanabe Pharma Corporation. T. Mune: None. K. Kaku: Speaker's Bureau; Astellas Pharma Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Boehringer Ingelheim Japan, Inc., Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation. Advisory Panel; Novo Nordisk. Consultant; Sanwa Kagaku Kenkyusho. Speaker's Bureau; Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co., Ltd. H. Kaneto: Research Support; Sumitomo Dainippon Pharma Co., Ltd., Taiho Pharmaceutical Co. Ltd., Boehringer Ingelheim Japan, Inc. Speaker's Bureau; Lilly, Sanofi, Boehringer Ingelheim Japan, Inc., Novo Nordisk, Sumitomo Dainippon Pharma Co., Ltd. Research Support; Abbott.
Aims: Effects of DPP-4 inhibitor or SGLT2 inhibitor on human β-cell function are not well understood, and there is no report showing the difference between the two agents. The aim of this study is to compare the effects of these drugs on β-cell function in patients with type 2 diabetes. Methods: The study protocol was approved by the IRB of Kawasaki Medical School (No. jRCTs061190008). A total of 103 patients met the inclusion criteria (age; 20 to 79 years, HbA1c; ≥7.0% and <9.0%). Subjects were randomly assigned to luseogliflozin (L) group (n=49) or teneligliptin (T) group (n=54) and received 24 wks of intervention followed by 1-2 wks of drug washout. The primary endpoint was the change in log-transformed (Ln) disposition index (DI) 0-120 from baseline. Subjects underwent 75gOGTT before and after treatment. Results: The main baseline backgrounds of L and T groups were as follows; age: 60.8±11.1 vs. 62.6±11.2 years (p=0.4), diabetes duration: 10.1±7.9 vs. 9.2±7.6 years (p=0.6), BMI: 27.0±4.2 vs. 27.2±5.4 kg/m2 (p=0.8), HbA1c: 7.6±0.4 vs. 7.5±0.5 % (p=0.5), DI 0-120: 0.80±0.60 vs. 0.92±0.59 (p=0.1). HbA1c levels were significantly decreased in both groups, but the amount of change was greater in the T group (-0.2%, p=0.02). Body weight was significantly decreased only in the L group, with a group difference of -2.5 kg (p<0.001). Ln DI 0-120 were improved in both groups: -0.46±0.66 to -0.15±0.59 (p=0.01) in L group and -0.26±0.60 to -0.02±0.60 (p=0.003) in T group. The change in Ln serum proinsulin/CPR ratio, a marker of β-cell dysfunction, was reduced in L group (1.63±0.63 to 1.56±0.68, p=0.16), but rather increased in T group (1.70±0.75 to 1.90±0.51, p=0.01), with significant difference between the 2 groups (-0.27; p=0.004). Conclusion: Improvement effects on DI 0-120 were almost identical between luseogliflozin and teneligliptin. On the other hand, burden on β-cells was mitigated only in luseogliflozin group. Disclosure M.Shimoda: Speaker's Bureau; Sanofi, Lilly, AstraZeneca, Ono Pharmaceutical Co., Ltd., Kowa Company, Ltd., Novo Nordisk, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., MSD Life Science Foundation, Mitsubishi Tanabe Pharma Corporation. A.Obata: None. T.Kimura: Speaker's Bureau; Sanwa Kagaku Kenkyusho, Kowa Research Institute, Inc., Taisho Pharmaceutical Holdings Co., Ltd., Boehringer Ingelheim Japan, Inc., Sumitomo Dainippon Pharma Co., Ltd., Sanofi, MSD Life Science Foundation, Lilly, Daiichi Sankyo, Novo Nordisk. F.Kawasaki: None. F.Tatsumi: Speaker's Bureau; Abbott Japan Co., Ltd., Kowa Company, Ltd., Novo Nordisk. S.Nakanishi: Speaker's Bureau; Boehringer Ingelheim Japan, Inc., Novo Nordisk, Sanofi, Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Daiichi Sankyo, Kowa Company, Ltd., Abbott, Mitsubishi Tanabe Pharma Corporation. T.Mune: None. K.Kaku: Advisory Panel; Novo Nordisk, Consultant; Sanwa Kagaku Kenkyusho, Speaker's Bureau; Astellas Pharma Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Boehringer Ingelheim Japan, Inc., Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co., Ltd. H.Kaneto: Research Support; Sumitomo Dainippon Pharma Co., Ltd., Taiho Pharmaceutical Co. Ltd., Boehringer Ingelheim Japan, Inc., Abbott, Speaker's Bureau; Lilly, Sanofi, Boehringer Ingelheim Japan, Inc., Novo Nordisk, Sumitomo Dainippon Pharma Co., Ltd. Y.Katakura: Speaker's Bureau; Abbott. M.Iwamoto: Speaker's Bureau; Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Boehringer Ingelheim Inc., Eli Lilly Japan K.K., Sumitomo Dainippon Pharma Co., Ltd. Y.Kimura: None. T.Anno: None. H.Isobe: None. Y.Iwamoto: Speaker's Bureau; Kowa Company, Ltd. Y.Fushimi: None. J.Sanada: Speaker's Bureau; Lilly, Kowa Company, Ltd. Funding Taisho Pharmaceutical Holdings Co., Ltd.
Grip strength (GS) as a surrogate for muscular strength, waist circumference (WC) as a surrogate marker of visceral fat, and body mass index (BMI) as a surrogate marker of obesity should also be considered markers for the management of risks associated with type 2 diabetes mellitus (T2DM). However, in terms of the management of T2DM in elderly patients, the accentuated heterogeneity of sarcopenic change might modify the associations between those factors and glycemic control. In this cross-sectional study, we aimed to clarify the impact of GS, WC, and BMI on hemoglobin A
Pituitary inflammation due to IgG4-related disease is a rare condition and is sometimes accompanied by central diabetes insipidus. Central diabetes insipidus produces a strong thirst sensation, which may be difficult to distinguish when complicated by salivary insufficiency. A 45-year-old man was admitted to our department for a thorough examination of his thirst and polyuria. He had suddenly developed these symptoms more than one year earlier and visited an oral surgeon. Swelling of the left submandibular gland, right parotid gland, and cervical lymph nodes had been observed. Since his IgG4 level was relatively high at 792 mg/dL and a lip biopsy showed high plasmacytoid infiltration around the gland ducts, he had been diagnosed with IgG4-related disease. He had started taking 0.4 mg/kg/day of prednisolone, and his chief complaint temporarily improved. However, since the symptom recurred, he was referred to our institution. After admission, to examine the cause of his thirst and polyuria, we performed a water restriction test, vasopressin loading test, hypertonic saline loading test and pituitary magnetic resonance imaging. Based on the findings, we diagnosed him with central diabetes insipidus due to IgG4-related hypophysitis. We increased the dose of prednisolone to 0.6 mg/kg/day and started 10 μg/day of intranasal desmopressin. His symptoms were subsequently alleviated, and his serum IgG4 level finally normalized. We should remember that IgG4-related disease can be accompanied by hypophysitis and that central diabetes insipidus is brought about by IgG4-related hypophysitis. This case report should remind physicians of the fact that pituitary inflammation due to IgG4-related disease is very rare and can be masked by symptoms due to salivary gland inflammation, which can lead to pitfalls in the diagnosis in clinical practice.
Background Immune checkpoint inhibitors (ICIs) cause a variety of immune-related adverse events (irAEs). Among them, thyroid dysfunction is most frequently observed. Patients with irAEs have higher survival rates than those without irAEs, but there is no certainty as to whether the degree of thyroid dysfunction is associated with treatment response or survival with ICIs. Method This is a single-center, retrospective, observational study. The study included 466 patients who received ICI at Kawasaki Medical School Hospital from September 1, 2014, to May 31, 2022 and evaluated the degree of abnormal thyroid function and survival and remission rates after treatment with ICIs. Primary hypothyroidism of less than 10 μIU/mL TSH was classified as grade 1, and primary hypothyroidism requiring more than 10 μIU/mL TSH or levothyroxine as grade 2-4. Result The mean age of the study participants was 68.2 ± 10.3 years, and the percentage of male participants was 72.6%. The frequency of ICI-induced thyroid dysfunction in the study participants was 28.2%. TSH levels were significantly higher in Grade 1 and Grades 2-4 when treated with ICI compared to NTF (p<0.0001). The survival rate at 1 year after ICI administration was significantly higher with 64.9% for grade 1 and 88.9% for grades 2-4 compared to 52.1% for NTF (p<0.0001). Cancer stage at the time of ICI administration did not differ among the groups (p=0.68). Nevertheless, the remission rate assessed by RECIST criteria was significantly higher in grades 2-4 compared to NTF (p<0.0001). Conclusion ICI-induced thyroid dysfunction was significantly correlated with survival, mean observation time, and treatment remission rate. It is important to monitor thyroid hormone levels regularly in patients receiving ICIs.
Acute necrotic esophagitis is characterized by blacking in the esophageal mucosa and is rarely accompanied by diabetes mellitus, especially under severe hyperglycemic conditions. Here we show a very rare case of a patient who had acute and extremely severe necrotic esophagitis accompanied by hyperglycemic hyperosmolar syndrome.
Abstract Aim Recently, the development of the oral glucagon‐like peptide‐1 receptor agonist semaglutide has drawn a great deal of attention. This study aimed to compare the effectiveness of oral glucagon‐like peptide‐1 receptor agonist semaglutide and dipeptidyl peptidase‐4 (DPP‐4) inhibitors on glycaemic control and several metabolic parameters in patients with type 2 diabetes mellitus over a 6‐month period. Methods Fifty‐nine participants were included, and we compared various clinical parameters between before and after switching from DPP‐4 inhibitors to oral semaglutide in ‘study 1’ (pre‐post comparison) and set the control group using the propensity score matching method in ‘study 2’. Results In ‘study 1’, 6 months after the switching, the glycated haemoglobin value was significantly reduced from 7.5% to 7.0%, and the body mass index was also decreased from 29.7 kg/m 2 to 28.8 kg/m 2 . Such effects were more clearly observed in participants whose glycaemic control was poor. In ‘study 2’, after 1:1 propensity score matching, 51 participants from each group were matched, and glycaemic control as well as body weight management were improved in the switching group compared with the DPP‐4 inhibitor continuation group over the 6‐month observation period. Conclusion In this study, including obese participants with poor glycaemic control, switching DPP‐4 inhibitors to oral semaglutide showed more beneficial effects on both glycaemic and weight control, irrespective of age, body weight and diabetes duration. Therefore, we should bear in mind that it would be better to start using an oral semaglutide in clinical practice, particularly in obese participants with poor glycaemic control with DPP‐4 inhibitors.
Intra-arterial CDDP is a highly effective method of achieving destruction of the primary tumor. From 1984 to 1988, 6 patients were treated with intraarterial CDDP (100 mg/m2). Five patients received three courses and one received two courses. The age of patients ranged from 11 to 27 years. According to the Enneking's surgical staging, all patients had stage II B disease. Analyzing the DNA ploidy pattern, one patient was near diploidy, and the others were hyperploid. Evidence of response was demonstrated by a decrease in tumor size (67%), a marginal sclerosis in soft tissue mass (83%), and a drop of serum alkaline phosphatase levels (100%). The CT scan was considered the most important parameter for determining response and defining the extent of tumor for wide excision. It is suspected that it is possible to apply a minimized wide resection for the primary tumor with a well-defined marginal sclerosis.
